Our understanding of eukaryotic gene function and regulation is very limited, in spite of recent advances in the description of eukaryotic genomes. The use of molecular and genetic techniques in parallel is one approach to the problem, but few higher organism systems are amenable to this approach. I propose to use the Drosophila gene-enzyme system of guanosine triphosphate cyclohydrolase as a model system for exploring gene structure, function and control. The approach will involve fine structure genetic mapping of mutations altering the gene product or expression in order to dissect the functional organization of the genetic unit. Genetic changes will be correlated with physical changes in the enzyme, messenger RNA and eventually the gene itself. The functions of specific parts of the genetic unit can then be identified and localized. GTP cyclohydrolase is a pteridine biosynthetic enzyme with a well-defined physiological role. Drosophila GTP cyclohydrolase has been partially purified and characterized. Its developmental profile, tissue distribution and physiological role indicate interesting regulatory features. Xanthine dehydrogenase, the product of the well-defined rosy gene, also functions in the pathway, offering opportunity for comparisons of structure, function and control in related genes, as well as for analysis of coordinate gene expression. Research necessary to develop this system includes genetic and cytological mapping of the GTP cyclohydrolase structural gene and genetic analysis of the surrounding region. A mutagenesis program will be initiated. Developmental and tissue distributions will be described in more detail. The protein will be further purified and characterized and anti-GTP cyclohydrolase antibody will be produced. Selection methods, prerequisites for fine structure mapping, will be devised. The experiments are intended to provide the genetic and biochemical characterizations that will be the foundation of a molecular genetic study. They will also provide the genetic markers needed for subsequent genetic manipulation and the protein for future sequence analysis.